Percutaneous administration of drugs has been intended to produce topical effects of the skin or subcutaneous tissues beneath the skin, such as sterilization, disinfection, analgesia, antipruritus, antiinflammation, and the like, while systemic effects have been expected by oral administration or injection.
Oral administration has problems in that the absorbed drug is susceptible to first-order metabolism in the liver and that the concentration of the drug in the body should temporarily be higher than necessary in order to obtain long-lasting effect. Further, oral administration of some drugs like indomethacin causes gastrointestinal side effects. On the other hand, administration through injection, though advantageous for obtaining rapid absorption, requires specialists, such as physicians.
In order to overcome the above-described problems, there have recently been proposed methods for obtaining systemic effects through percutaneous administration. Percutaneous administration of drugs has various merits, such as that: the release of the active ingredient can easily be sustained; the concentrations of the active ingredient in the body are controllable; the drug enters from the skin directly into the blood flow, and is not, therefore, susceptible to first-order metabolism in the liver; and the like.
However, since the skin normally possesses a barrier function to prevent entrance of foreign matter into the interior of the body, the purpose of percutaneous administration has traditionally been limited to topical effects. Hence, when drugs are percutaneously administered aiming at systemic effects, it is required to use a percutaneous absorption-accelerating agent. In recent years, various absorption-accelerating agents have been proposed. For example, U.S. Pat. No. 3,551,554 discloses dimethyl sulfoxide, and, in addition, dimethylacetamide, dimethylformamide, methyldecyl sulfoxide, etc.
Additional examples of absorption-accelerating agents are ethyl alcohol, isopropyl alcohol or isopropyl palmitate in combination with a lower alkylamide, e.g., dimethylacetamide as disclosed in U.S. Pat. No. 3,472,431; combinations of 2-pyrrolidone and appropriate oils or esters of straight chain fatty acids and alcohols as disclosed in U.S. Pat. No. 4,017,641; and the like. However, these known agents are still unsatisfactory in terms of effects, safety, and feeling of use.